Dicyclohexylcarbodiimide → HCID 86675669, compound

HRID 1914503Notes

Reaction equation

HRID 1914503 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH:13]([CH3:15])[CH3:14])[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(N=C=NC2CCCCC2)CCCCC1.[CH2:31]([O:38][C@H:39]1[C@H:44]([O:45][CH2:46][C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[C@@H:43]([O:53][CH2:54][C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[C@H:42]([C:61]2[CH:66]=[CH:65][C:64]([CH2:67][CH3:68])=[C:63]([CH2:69][C:70]3[CH:79]=[CH:78][C:73]4[O:74][CH2:75][CH2:76][O:77][C:72]=4[CH:71]=3)[CH:62]=2)[O:41][C@@H:40]1[CH2:80]O)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>CN(C=O)C.CN(C1C=CN=CC=1)C>[CH2:31]([O:38][C@H:39]1[C@H:44]([O:45][CH2:46][C:47]2[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=2)[C@@H:43]([O:53][CH2:54][C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[C@H:42]([C:61]2[CH:66]=[CH:65][C:64]([CH2:67][CH3:68])=[C:63]([CH2:69][C:70]3[CH:79]=[CH:78][C:73]4[O:74][CH2:75][CH2:76][O:77][C:72]=4[CH:71]=3)[CH:62]=2)[O:41][C@@H:40]1[CH2:80][O:11][C:10](=[O:12])[C@H:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH:13]([CH3:15])[CH3:14])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

6

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 637605(2R)-2-(((tert-butoxy)carbonyl)amino)-3-methylbutanoic acidHCID 70872898HCID 70872898, compound

Product 1

HCID 86675669HCID 86675669, compoundYield 87.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of (R)-2-tert-butoxycarbonylamino-3-methyl-butyric acid (6.3 g, 29.1 mmol) in DMF (40 ml) was added N,N′-dicyclohexylcarbodiimide (6.0 g, 29.1 mmol). After stirring for 30 min at room temperature, reaction mixture was cooled to 0° C., added a solution of {(2R,3R,4R,5S,6S)-3,4,5-tris-benzyloxy-6-[3-(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-4-ethyl-phenyl]-tetrahydro-pyran-2-yl}-methanol (4.0 g, 5.8 mmol) in DMF (20 ml) followed by DMAP (360 mg, 2.9 mmol) and stirred at ambient temperature for overnight. Reaction was quenched by the addition of water (150 ml) and extracted with ethyl acetate (2×80 ml). Combined organic layers were washed with water (100 ml), brine (100 ml), dried over sodium sulfate, concentrated and purified by silica gel column chromatography to give 4.5 g of (R)-2-tert-butoxycarbonylamino-3-methyl-butyric acid (2R,3R,4R,5S,65)-3,4,5-tris-benzyloxy-6-[3-(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-4-ethyl-phenyl]-tetrahydro-pyran-2-ylmethyl ester as a colorless oil.

Workup

  1. customreaction mixture
  2. temperaturewas cooled to 0° C.
  3. stirringstirred at ambient temperature for overnight
  4. customReaction
  5. customwas quenched by the addition of water (150 ml)
  6. extractionextracted with ethyl acetate (2×80 ml)
  7. washCombined organic layers were washed with water (100 ml), brine (100 ml)
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-83282ab1c732482ea0e03568d99310b4
Source dataset
uspto-grants-2013_12
Patent number
US08614195B2

Reaction notes

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